This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hyperoxic contrast (increasing the inspired fraction of oxygen >21%) produces positive contrast enhancement in T2*-weighted images in brain tissue and has been used to calculate cerebral blood volume and to standardize signal changes in BOLD fMRI experiments. The increase in venous blood oxygenation is due to excess dissolved oxygen carried in the plasma of arterial blood, which during hyperoxia contains completely saturated hemoglobin. While it is known that molecular oxygen is paramagnetic and that increased concentrations significantly reduce T1, the effect in heavily T2*-weighted images is generally considered to be negligible when compared to the effects of BOLD contrast, especially at low FiO2 levels. We have found in our preliminary studies using hyperoxic contrast in a whole brain EPI study at 3T that, although positive contrast enhancement dominates most regions, the inferior regions of the brain show significant negative contrast enhancement in strongly T2*-weighted images, even at low oxygen concentration (FiO2<0.6). These regions showing negative contrast have a relatively high fraction of arterial cerebral blood volume, since they contain large arteries that feed the brain. We believe that this negative contrast is at least in part due to the shortening of T2* in arterial blood due excess paramagnetic molecular oxygen dissolved in the plasma.